Environmental Variations in Mycobacterium ulcerans Transcriptome: Absence of Mycolactone Expression in Suboptimal Environments

Abstract

Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen Mycobacterium ulcerans (MU). Neither the ecological niche nor the exact mode of transmission of MU are completely elucidated. However, some environmental factors, such as the concentration in chitin and pH values, were reported to promote MU growth in vitro. We pursued this research using next generation sequencing (NGS) and mRNA sequencing to investigate potential changes in MU genomic expression profiles across in vitro environmental conditions known to be suitable for MU growth. Supplementing the growth culture medium in either chitin alone, calcium alone, or in both chitin and calcium significantly impacted the MU transcriptome and thus several metabolic pathways, such as, for instance, those involved in DNA synthesis or cell wall production. By contrast, some genes carried by the virulence plasmid and necessary for the production of the mycolactone toxin were expressed neither in control nor in any modified environments. We hypothesized that these genes are only expressed in stressful conditions. Our results describe important environmental determinants playing a role in the pathogenicity of MU, helping the understanding of its complex natural life cycle and encouraging further research using genomic approaches.

A need for null models in understanding disease transmission: the example ofMycobacterium ulcerans(Buruli ulcer disease)

“…This is probably not the case of all species that have been reported to carry MU (Table 1 and Table S1, Supporting Information). Given the importance of chitin to the development of free-living MU (Sanhueza et al 2016(Sanhueza et al , 2019, most of these carriers should be able to support the development of MU due to the presence of chitinous compounds in their exoskeleton (e.g. insect larvae and snails) or fur (e.g.…”

“…All of these findings indicate an aerobic environment where there is protection from UV and high salinity (Doig 2012). Lab experiments on MU growth have shown that mycobacterium colonies benefit fromchitin-rich substrates (Sanhueza et al 2019), which suggests a potential association with organisms or substrates with chitin composition.…”

Impact of Temperature and Oxygen Availability on Gene Expression Patterns of Mycobacterium ulcerans

“…One study showed that transcription of several key mycolactone biosynthetic genes is driven by a SigA-like promoter ( 24 ); however, the study did not determine environmental or growth-phase signals inducing mycolactone gene expression. An in vitro study showed mycolactone genes downregulated in response to various sugar sources ( 25 ), and other research showed that nutrient availability (chitin versus calcium) regulates several metabolic pathways in M. ulcerans ; however, mycolactone toxin was not expressed in these nutrient-abundant environments, suggesting that its expression may be regulated mainly under stressful conditions ( 26 ).…”